Cognitive Dysfunction In Multiple Sclerosis Research Articles

Neurological update: cognitive rehabilitation in multiple sclerosis.

Cognitive impairment is a common and debilitating symptom in multiple sclerosis (MS). There is limited evidence that disease-modifying therapies are effective in treating cognitive dysfunction. Cognitive rehabilitation is a promising approach to treat cognitive dysfunction in MS, gaining empirical support over the last 10years. The current review will provide a brief overview of cognitive rehabilitation in MS. Overall, there is evidence that cognitive rehabilitation programs (either restorative or compensatory) are efficacious in treating MS-related cognitive dysfunction. Clinicians should consider this low-cost, low-risk, yet effective treatment approach for their patients.

Staging and stratifying cognitive dysfunction in multiple sclerosis

Background: The sequence in which cognitive domains become impaired in multiple sclerosis (MS) is yet to be formally demonstrated. It is unclear whether processing speed dysfunction temporally precedes other cognitive impairments, such as memory and executive function. Objective: Determine the order in which different cognitive domains become impaired in MS and validate these findings using clinical and vocational outcomes. Methods: In a longitudinal sample of 1073 MS patients and 306 healthy controls, we measured performance on multiple, consensus-standard, neurocognitive tests. We used an event-based staging approach to model the sequence in which cognitive domains become impaired. Linear and logistic mixed-effects models were used to explore associations between stages of impairment, neurological disability, and employment status. Results: Our model suggested that the order of impairments was as follows: processing speed, visual learning, verbal learning, working memory/attention, and executive function. Stage of cognitive impairment predicted greater neurological disability, β = 0.16, SE = 0.02, p < 0.001, and probability of unemployment, β = 1.14, SE = 0.001, p < 0.001. Conclusion: This is the first study to introduce a cognitive staging and stratification system for MS. Findings underscore the importance of using the Symbol Digit Modalities Test in routine screening for cognitive impairment and memory testing to assess patients later in disease evolution.

A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis.

Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results. Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = −8.54; 95%CI = −15.51, −1.57; and Coeff = −0.11; 95%CI = −0.20, −0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. Conclusions. In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function.

Assessment of Cerebrovascular Dynamics and Cognitive Function with Acute Aerobic Exercise in Persons with Multiple Sclerosis.

Cognitive dysfunction in multiple sclerosis (MS) may partially stem from inadequate cerebral blood flow. Cerebral blood flow and cognitive function improve with aerobic exercise in healthy adults. The effect of aerobic exercise on cerebrovascular hemodynamics and cognitive performance in persons with MS is unclear. The acute effect of aerobic exercise versus quiet rest on cerebrovascular hemodynamics and cognitive performance in relapsing-remitting MS was examined. Sixteen adults with relapsing-remitting MS underwent cerebrovascular hemodynamics and cognitive performance testing before, 2 minutes after, and 30 minutes after aerobic exercise (20-minute treadmill walking, 60% peak oxygen consumption) and a time-matched seated control. Brachial blood pressure was obtained via an oscillometric cuff. Right middle cerebral artery (MCA) blood velocity was measured via transcranial Doppler and used to calculate mean velocity, pulsatility index (PI), and conductance. Carotid artery stiffness was measured via ultrasonography and tonometry. Cognitive performance (accuracy, reaction time) was assessed using a modified flanker task. Exercise elicited significant increases in mean pressure and carotid artery stiffness and decreases in MCA conductance at 2 minutes after exercise, which subsided by 30 minutes (P < .05). Exercise did not significantly alter MCA PI. Flanker reaction time decreased during posttesting in both conditions (P < .05). There were no condition × time interactions for cognitive performance. Persons with MS seem resilient to exercise-induced acute changes in MCA PI despite transient carotid stiffening, potentially via reductions in MCA conductance. These data suggest that changes in cognitive performance after acute aerobic exercise are not directly related to transient cerebrovascular responses in persons with MS.

Event-related potentials and deep grey matter atrophy in multiple sclerosis: Exploring the possible associations with cognition

BackgroundEvent-related potentials (ERPs) have been proposed as a neurophysiological biomarker to capture cognitive dysfunction in multiple sclerosis (MS). Few studies have evaluated the relationships between ERPs and brain atrophy as known marker of structural brain damage related to cognitive impairment (CI). ObjectivesTo explore the relationships of brain atrophy, including of the cortex and deep grey matter, with ERP abnormalities and cognitive function, as defined using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). ResultsSeventy-eight patients with relapsing-remitting MS were enroled, of which 38 (48.7%) had CI. Independent t-test comparisons of the ERP parameters found a significant difference in P300 wave latency, with a latency of 343.7 ± 32.6 ms in the CI group vs. 320.3 ± 16.5 ms in the cognitively preserved (CP) group (p = 0.001). Significant differences in the MRI measurements, including the cortex (p = 0.02) and deep grey matter structures [thalamus (p = 0.001), amygdala (p = 0.030), and nucleus accumbens (p = 0.004)) were observed, with lower measurements in the CI group. Regression models were also performed to explore the impact of brain volumes on ERP parameters. This showed a relationship between P300 latency and the lower amygdala (p = 0.02) and hippocampus (p = 0.03) volumes, while the amplitude of the P300 was significantly associated with a lower cortex volume (p = 0.01). ConclusionCortex volume emerged as the most significant predictor of the P300 amplitude. The amygdala and hippocampal volumes were found to influence P300 latency, highlighting the role of deep grey matter atrophy in ERPs for the first time. The combination of structural MRI and neurophysiological techniques, sensitive to diverse aspects of MS pathology, could improve the understanding of CI in MS and its neurodegenerative and inflammatory substrate.

Content Validity of an Integrated Yoga Module for Practice During Remission in Relapsing-Remitting Multiple Sclerosis Patients.

Background:Some investigations point to the beneficial effects of yoga in alleviating the motor and cognitive dysfunctions in multiple sclerosis (MS) patients by using varying combinations of physical, breathing, and meditative practices of yoga. There is a need for a validated yoga module with a holistic approach that can be used as a standardized protocol by researchers and therapists.Purpose:To develop and validate an integrated yoga module for practice in relapsing–remitting MS patients to improve their quality of life.Methods:We did a thorough review of the literature for the development of the yoga module. We formed an expert group with 24 experts and a neurologist and used two rounds of interactive Delphi method to combine their opinion to obtain content validity of the module through online structured questionnaire prepared for the purpose on a Google Form. We incorporated all suggestions obtained by the experts. The final module (60 min per session, twice a day, five days per week) included warm-up exercises, customized asanas, relaxation techniques, and OM meditation. Advice on yogic diet and discussion using yogic concepts for stress management also form a part of the holistic approach to yoga lifestyle modification.Results:Analysis divulged that 30 out of 39 practices exhibited a content validity ratio value greater than or equal to 0.42.Conclusion:The study has shown good content validity of the integrated yoga module. Future clinical studies are being planned to rule the feasibility and reliability of this module.

The correlation between motor and cognitive dysfunction in multiple sclerosis

The correlation between motor and cognitive dysfunction in multiple sclerosis Konstantin K. Mineev, Andrey M. Petrov, Marina V. Votintseva, Igor' D. Stolyarov N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences, St. Petersburg, Russia Introduction. Impaired ambulation is one of the most common and disabling symptoms in multiple sclerosis (MS). Cognitive impairment occurs in the early stages of MS and worsens as the disease progresses. The aim of the study was to investigate the correlation between walking speed and distance and the severity of neurological and cognitive impairment in MS. Materials and methods. We examined 59 patients with relapsing-remitting MS in clinical remission. Motor function was evaluated using the timed 25-foot walk (mobility and leg function performance test based on a timed 25-walk), the nine-hole peg test was used to assess upper limb motor function, the Ashworth Scale was used to evaluate lower limb spasticity, the EDSS scale (pyramidal function) was used to evaluate gait spasticity, and tests for sustained attention, counting skills, short-term and delayed memory, mathematical logic, speech fluency, and sensorimotor reaction speed were used to assess cognitive function. Results. In MS, an increased score on the disability scale was accompanied by increased motor disturbances, reduced distance covered when walking, decreased walking speed, and slower hand movements. Increased spasticity was accompanied by a deterioration in cognitive test performance. The study showed a high correlation between spasticity and reduced computational abilities, mathematical logic, and the ability to remember shapes. Walking distance correlated with attention span and short-term and delayed memory while walking speed characteristics correlated with the movement speed of the non-dominant hand. Slower hand activity correlated with the conducted cognitive tests, with the most significant differences recorded in the non-dominant hand. Conclusion. The study results indicate significant and varied motor and cognitive dysfunction in MS patients, caused by damage to both the conduction pathways in the brain and spinal cord and the cortical grey matter. The obtained data on the close correlation between motor and cognitive impairments allow us to better understand the mechanisms of MS development and to apply this knowledge in clinical practice.

Brain dysconnectivity relates to disability and cognitive impairment in multiple sclerosis.

The pathophysiology of cognitive dysfunction in multiple sclerosis (MS) is still unclear. This magnetoencephalography (MEG) study investigates the impact of MS on brain resting‐state functional connectivity (rsFC) and its relationship to disability and cognitive impairment. We investigated rsFC based on power envelope correlation within and between different frequency bands, in a large cohort of participants consisting of 99 MS patients and 47 healthy subjects. Correlations were investigated between rsFC and outcomes on disability, disease duration and 7 neuropsychological scores within each group, while stringently correcting for multiple comparisons and possible confounding factors. Specific dysconnections correlating with MS‐induced physical disability and disease duration were found within the sensorimotor and language networks, respectively. Global network‐level reductions in within‐ and cross‐network rsFC were observed in the default‐mode network. Healthy subjects and patients significantly differed in their scores on cognitive fatigue and verbal fluency. Healthy subjects and patients showed different correlation patterns between rsFC and cognitive fatigue or verbal fluency, both of which involved a shift in patients from the posterior default‐mode network to the language network. Introducing electrophysiological rsFC in a regression model of verbal fluency and cognitive fatigue in MS patients significantly increased the explained variance compared to a regression limited to structural MRI markers (relative thalamic volume and lesion load). This MEG study demonstrates that MS induces distinct changes in the resting‐state functional brain architecture that relate to disability, disease duration and specific cognitive functioning alterations. It highlights the potential value of electrophysiological intrinsic rsFC for monitoring the cognitive impairment in patients with MS.

The impact of deep grey matter volume on cognition in multiple sclerosis

BackgroundCognitive dysfunctions are very frequent in people living with multiple sclerosis (MS). Several studies have previously indicated grey matter (GM) atrophy as useful predictor of patients’ cognitive impairment. However, considerable uncertainty exists about the possible impact of deep grey matter volumes on cognition. This study aimed to evaluate the relationship of the subcortical (sc) GM volumes with the presence and severity of global and selective cognitive impairment in MS. MethodsA group of MS patients with relapsing remitting course were enrolled. Patients underwent a neuropsychological evaluation by using the Brief Repeatable Battery of Neuropsychological Tests (BRBN) and the Delis–Kaplan Executive Function System Sorting Test (D-KEFST); z scores were estimated and items with z score below 2 standard deviation were considered failed. Thus, brain MRIs images were acquired and measurements of whole brain (WB), white matter (WM), and cortical grey matter (GM) were obtained by SIENAX. After FIRST tool segmentation, volumes of subcortical GM structures were also estimated. ResultsThe sample included 50 MS patients, of which 16/50 (32%) subjects were cognitively impaired. Multiple regression analyses found a significant association of severity of cognitive impairment, defined as number of failed neuropsychological tests, with lower volumes of cortex (p=0.003), thalamus (p=0.009), caudate (p=0.011), putamen (p=0.020), pallidus (p=0.012) and hippocampus (p=0.045), independently from other MS features. In addition, an association between accumbens volume and D-KEFS ST FSC and D-KEFS ST FSD z scores was observed (p<0.03). ConclusionsOur results indicated that volumes of several scGM structures, and in particular of thalamus, contribute to determine cognitive dysfunctions in MS, mainly influencing the executive functioning. Further investigations in larger MS cohorts with cognitive impairment are necessary to better understand the structural brain damage underlying this “invisible disability”.

Baseline cerebral metabolism predicts fatigue and cognition in Multiple Sclerosis patients

BackgroundCerebral metabolic rate of oxygen (CMRO2), a measure of global oxygen metabolism, reflects resting cellular activity. The mechanisms underlying fatigue and cognitive dysfunction in multiple sclerosis (MS) remain unknown. If fatigue indeed reflects ongoing autoimmune activity and cortical reorganization, and cognitive decline is the result of gray matter atrophy and white matter degeneration, we postulate that changes in CMRO2 should reflect disease activity and predict these symptoms. ObjectiveWe sought to utilize T2-Relaxation-Under-Spin-Tagging (TRUST) and phase-contrast (PC) MRI to measure global CMRO2 to understand its relationships to white matter microstructure, fatigue and cognitive dysfunction. MethodsWe measured venous oxygenation (TRUST) and cerebral blood flow (PC-MRI) in superior sagittal sinus to calculate global CMRO2 and diffusion tensor imaging (DTI) to evaluate white matter microstructure in healthy controls (HC) and MS patients. Participants underwent neuropsychological examinations including Modified Fatigue Impact Scale (MFIS) and Symbol-Digit-Modalities Test (SDMT). ResultsWe observed lower CMRO2 in MS patients compared to HC. After controlling for demographic and disease characteristics (i.e., age, education, disability, lesion volume), CMRO2 predicted increased fatigue (MFIS) and reduced cognitive performance (SDMT) in MS patients. Finally, MS patients with higher CMRO2 have reduced FA in normal-appearing white-matter. ConclusionAltogether, these results suggest that increased CMRO2 reflects ongoing demyelination and autoimmune activity which plays an important role in both fatigue and cognitive dysfunction.

Melatonin improves memory defects in a mouse model of multiple sclerosis by up-regulating cAMP-response element-binding protein and synapse-associated proteins in the prefrontal cortex.

Multiple sclerosis is a progressive autoimmune disorder of the myelin sheath and is the most common inflammatory disease of young adults. Up to 65% of multiple sclerosis patients have cognitive impairments such as memory loss and difficulty in understanding and maintaining attention and concentration. Many pharmacological interventions have been used to reverse motor impairments in multiple sclerosis patients; however, none of these drugs improve cognitive function. Melatonin can diffuse through the blood-brain barrier and has well-known antioxidant and anti-inflammatory properties with almost no side effects; it is, therefore, a promising neuroprotective supplement for many neurological diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, and fibromyalgia. However, only some researches have assessed the effect of melatonin on cognitive dysfunction in multiple sclerosis. Here, we evaluated the effects of melatonin supplementation on memory defects induced by cuprizone in a mouse model of multiple sclerosis. Cuprizone (400 mg/kg) and melatonin (80 mg/kg) were administered to SWR/J mice daily for 5 weeks. Open field, tail-flick, and novel object recognition behavioral tests were performed. Also, expression of cAMP-response element-binding protein, synaptophysin, and postsynaptic density protein 95 were measured in the prefrontal cortex. Melatonin significantly improved the memory defects induced by cuprizone toxicity by up-regulating cAMP-response element-binding protein and by increasing expression of the synapse-associated synaptophysin and postsynaptic density protein 95 genes in the prefrontal cortex. These results indicate that melatonin may provide protective effects against memory impairments associated with multiple sclerosis.

The efficacy of active physical exercises in comprehensive cognitive rehabilitation of pediatric and adult patients with multiple sclerosis

Cognitive dysfunction in multiple sclerosis (MS) is a disabling factor and extends to the processes of memory, attention, verbal and logical thinking, visual-spatial, and motor skills. 40-70% of patients have a decrease in the rate of information processing, dysfunction of executive functions, and decrease in the quality of training. Cognitive dysfunction is also often reduced quality of life with MS. The most common methods of non-drug cognitive function correction are cognitive rehabilitation and exercise. This article reviews current research on the positive effects of regular physical activity on the cognitive functions of adults and children with MS.

Functional and structural connectivity substrates of cognitive performance in relapsing remitting multiple sclerosis with mild disability.

Multiple Sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), which can lead to severe cognitive impairment over time. Magnetic resonance imaging (MRI) is currently the best available biomarker to track MS pathophysiology in vivo and examine the link to clinical disability. However, conventional MRI metrics have limited sensitivity and specificity to detect direct associations between symptoms and their underlying CNS substrates. In this study, we aimed to investigate structural and resting state functional connectomes and subnetworks associated with neuropsychological (NP) performance using a graph theoretical approach. A comprehensive NP test battery was administered in a sample of patients with relapsing remitting MS (RRMS) and mild disability [n=33, F/M=20/13, age=40.9±9.7, median [Expanded Disability Status Scale] (EDSS)=2, range =0-4] and compared to healthy controls (HC) [n=29, F/M=19/10, age=41.0±8.5] closely matched for age, sex, and level of education. The NP battery comprised the most relevant domains of cognitive dysfunction in MS including attention, processing speed, verbal and spatial learning and memory, and executive function. While standard MRI metrics showed good correlations with TAP Alertness test, disease duration and neurological exams, structural networks showed closer associations with 9-hole peg test and cognitive performances. Decreased graph strength was associated with two out of the 5 NP tests in the spatial learning and memory domain specified by BVMT [Sum 1-3] and BVMT [Recall], and with also SDMT which is one out of the 9 NP tests in the attention/processing speed domain, while no correlation was found between these scores and functional connectivity. Nodal strength was decreased in all subnetworks based on Yeo atlas in patients compared to HC; however, no difference was observed in nodal level of functional connectivity between the groups. The difference in structural and functional nodal connectivity between the groups was also observed in the relationship between structural and functional connectivity within the groups; the relationship between nodal degree and nodal strength was reversed in patients but positive in controls. On a nodal level, structural and functional networks (mainly the default mode network) were correlated with more than one cognitive domain rather than one specific network for each domain within patients. Interestingly, poorer cognitive performance was mostly correlated with increased functional connectivity but decreased structural connectivity in patients. Increased functional connectivity in the default mode network had both positive as well as negative associations with verbal and spatial learning and memory, possibly indicating adaptive and maladaptive mechanisms. In conclusion, our results suggest that cognitive performance, even in patients with RRMS and very mild disability, may reflect a loss of structural connectivity. In contrast, widespread increases in functional connectivity may be the result of maladaptive processes.

Analysis of brain functional connectivity network in MS patients constructed by modular structure of sparse weights from cognitive task-related fMRI.

Cognitive dysfunction in multiple sclerosis (MS) seems to be the result of neural disconnections, leading to a wide range of brain functional network alterations. It is assumed that the analysis of the topological structure of brain connectivity network can be used to assess cognitive impairments in MS disease. We aimed to identify these brain connectivity pattern alterations and detect the significant features for the distinction of MS patients from healthy controls (HC). In this regard, the importance of functional brain networks construction for better exhibition of changes, inducing the improved reflection of functional organization structure should be precisely considered. In this paper, we strove to introduce a framework for modeling the functional connectivity network by considering the two most important intrinsic sparse and modular structures of brain. For the proposed approach, we first derived group-wise sparse representation via learning a common over-complete dictionary matrix from the aggregated cognitive task-based functional magnetic resonance imaging (fMRI) data of all subjects of the two groups to be able to investigate between-group differences. We then applied the modularity concept on achieved sparse coefficients to compute the connectivity strength between the two brain regions. We examined the changes in network topological properties between relapsing-remitting MS (RRMS) and matched HC groups by considering the pairwise connections of regions of the resulted weighted networks and extracting graph-based measures. We found that the informative brain regions were related to their important connectivity weights, which could distinguish MS patients from the healthy controls. The experimental findings also proved the discrimination ability of the modularity measure among all the global features. In addition, we identified such local feature subsets as eigenvector centrality, eccentricity, node strength, and within-module degree, which significantly differed between the two groups. Moreover, these nodal graph measures have been served as the detectors of brain regions, affected by different cognitive deficits. In general, our findings illustrated that integration of sparse representation, modular structure, and pairwise connectivity strength in combination with the graph properties could help us with the early diagnosis of cognitive alterations in the case of MS.

Thalamic nuclei volumes as markers of clinical disability and cognitive dysfunction in multiple sclerosis (P5.2-069)

Thalamic nuclei volumes as markers of clinical disability and cognitive dysfunction in multiple sclerosis (P5.2-069)

A clinical screening tool for objective and subjective cognitive disorders in multiple sclerosis.

Cognitive dysfunction is common in multiple sclerosis (MS). Deficits can affect attention, concentration, planning, and memory. They can have severe functional consequences in many domains. Cognitive complaints are frequently associated with other confounding factors (fatigue, anxiety, depression, or treatment side effects). In most cases, cognitive assessment is proposed after a spontaneous complaint, but determining the extent of discomfort perceived by the patient, the influence of coexisting factors, or the optimal timing for a more complete neuropsychological assessment is difficult. The objective of this work was to evaluate the feasibility and relevance of a fast global assessment of both objective and subjective cognitive dysfunction in MS. MS patients underwent a brief cognitive assessment including 7 visual analogue scales (VASs) asking about the patient's subjective level of discomfort in various domains, a memory test (Barbizet's lion story), a commonly used test of information processing speed (Symbol Digit Modalities Test [SDMT]) and self-reporting questionnaires for fatigue and mood (Fatigue Severity Scale [FSS] and Hospital Anxiety and Depression Scale [HADS]). Spearman correlation coefficients among scores were estimated. The mean age of the 73 patients included was 48.3 (SD 11.1) years; 78% were females and 52.8% had the remittent-recurrent MS form, 8.3% the primary progressive form, and 38.9% the secondary progressive form. In less than 20min, this brief cognitive assessment was able to identify symptoms and quantify discomfort level. Symptoms of fatigue and anxiety frequently coexisted with cognitive complaints. We found modest correlations between scores on the VAS fatigue and the FSS and between scores on the VAS mood and the HADS. Analytical evaluation revealed that most patients had similar SDMT and recall profiles; however, a small proportion showed a dissociation between these 2 tests, which validated the inclusion of both tests in the assessment. Accounting for coexisting factors (e.g., anxiety and fatigue) and their functional repercussions is essential for prioritizing these problems within the context of multidisciplinary patient treatment. Considering the possible multifactorial character of cognitive dysfunction in MS, it is essential to ask patients about their experiences and to take into account cognitive complaints in the follow-up of patients. The assessment tool we propose is simple and easy to use in a clinical setting and provides the information necessary for requesting (or not) a more complete neuropsychological assessment.

Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes.

ObjectiveBrain atrophy has been correlated with objective cognitive dysfunction in multiple sclerosis but few studies have explored self-reported subjective cognitive concerns and their relationship to brain volume changes. This study explores the relationship between subjective cognitive concerns in multiple sclerosis and reduced brain volume in regions of interest implicated in cognitive dysfunction.MethodsA total of 158 patients with multiple sclerosis completed the Quality of Life in Neurologic Disorders Measures (Neuro-QoL) short forms to assess subjective cognitive concerns and underwent brain magnetic resonance imaging. Regional brain volumes from regions of interest implicated in cognitive dysfunction were measured using NeuroQuant automated volumetric quantitation. Linear regression was used to analyze the relationship between subjective cognitive concerns and brain volume.ResultsControlling for age, disease duration, gender, depression and fatigue, increased subjective cognitive concerns were associated with reduced thalamic volume (standardized β = 0.223, t150 =2.406, P = 0.017) and reduced cortical gray matter volume (standardized β = 0.240, t150 = 2.777, P = 0.006). Increased subjective cognitive concerns were not associated with any other regions of interest that were analyzed.ConclusionsSubjective cognitive concern in MS is associated with reduced thalamic and cortical gray matter volumes, areas of the brain that have been implicated in objective cognitive impairment. These findings may lend neuroanatomical significance to subjective cognitive concerns and patient-reported outcomes as measured by Neuro-QoL.

Phosphodiesterase 7B1 as Therapeutic Target for Treatment of Cognitive Dysfunctions in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune, chronic degenerative neuroinflammatory disorder affecting younger age groups of the United States of America and Europe. MS prevalence studies in India have shown that India is no longer a low-risk zone. Many studies have shown the seriousness of cognitive impairments (CIs) and its types caused in MS. In this review, the pathological basis for CI in various stages of MS was reviewed and revealed to provide a basis for the treatment. Role of phosphodiesterase 7B1 (PDE7B1) inhibitors in treating CI related to MS were also stated in this review. The literature for this review was collected from PubMed and Embase.

Higher Cortical Dysfunction Resembling Corticobasal Syndrome in 2 Patients with Multiple Sclerosis

The cognitive dysfunction in Multiple Sclerosis is classically defined as deficits in executive function, processing speed and memory. This pattern has been termed “subcorticaldy sfunction”. However, a growing body of literature suggests that there is cortical disruption in patients with Multiple Sclerosis and higher cortical dysfunction may manifest as symptoms. Here is presented two patients with Multiple Sclerosis who developed symptoms suggestive of Corticobasal syndrome, a disorder of higher cortical dysfunction due to a number of different pathologic substrates.

Relation of serum levels of homocysteine, vitamin B12 and folate to cognitive functions in multiple sclerosis patients

ABSTRACTBackground: Hyperhomocysteinemia, vitamin B12 and folate deficiency have been linked to cognitive dysfunction in multiple sclerosis (MS) patients.Objective: This study aimed to investigate the relation of serum homocysteine (Hcy), vitamin B12 and folate to cognitive functions in MS patients.Subjects and Methods: Forty-five MS patients and twenty matched healthy controls were included. Subjects were submitted to cognitive assessment using a selected psychometric battery and measurement of serum levels of homocysteine, B12 and folic acid.Results: MS patients showed significant worse performance in cognitive scales compared to controls (P ≤ 0.05). Serum homocysteine, vitamin B12 and folate showed no significant difference between patients and controls (P > 0.05). Serum homocysteine was negatively correlated with total score of Addenbrooke's Cognitive Examination (ACE), paced auditory serial addition test and controlled oral word association test scores. Serum vitamin B12 was positively correlated with ACE language, visuospatial and total scores and negatively correlated with trail making B score. Serum folate was significantly positively correlated with ACE language and total scores. Homocysteine was the only significant predictor for cognitive impairment in MS patients.Conclusion: Serum homocysteine may play a role in cognitive dysfunction in MS patients.